TY - JOUR
T1 - Early phase dynamics of traceable mCherry fluorescent protein-carrying HIV-1 infection in human peripheral blood mononuclear cells-transplanted NOD/SCID/Jak3-/- mice
AU - Higashi-Kuwata, Nobuyo
AU - Ogata-Aoki, Hiromi
AU - Hattori, Shin ichiro
AU - Hayashi, Hironori
AU - Danish, Matthew
AU - Aoki, Manabu
AU - Shiotsu, Chiemi
AU - Kawamura, Tatsuyoshi
AU - Ihn, Hironobu
AU - Kobayashi, Hisataka
AU - Okada, Seiji
AU - Mitsuya, Hiroaki
N1 - Funding Information:
The authors thank Y. Yonemura, R. Kariya, and K. Maeda for valuable comments and suggestions. The present work was supported in part by a Grant for Development of Novel Drugs for Treating HIV-1 Infection and AIDS from Japan Agency for Medical Research and Development, Grants from Japan Society for the Promotion of Sciences, a Grant from National Center for Global Health & Medicine, and a Grant from the Intramural Research Program of Center for Cancer Research, National Cancer Institute, National Institutes of Health.
PY - 2017/8
Y1 - 2017/8
N2 - We attempted to elucidate early-phase dynamics of HIV-1 infection using replication-competent, red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL (HIVJR-FLmC) and NOD/SCID/Jak3-/- mice transplanted with Individual-A's human peripheral blood mononuclear cells (hPBMC)(hNOJ mice). On day 7 following HIVJR-FLmC inoculation, mCherry-signal-emitting infection foci were readily identified in the subserosa of 10 of 10 HIVJR-FLmC-inoculated hNOJ mice, although infection foci were not located without the mCherry signal in unlabeled HIV-1JR-FL-inoculated mice (n = 6). Even on day 14, infection foci were hardly located in the unlabeled HIV-1JR-FL-inoculated mice, while in all of 7 HIVJR-FLmC-inoculated hNOJ mice examined, mCherry-signal-emitting lymph nodes were easily identified, in which active viral replication was present. On day 14, a significantly larger number of mesenteric lymph nodes were seen in HIVJR-FLmC-exposed hNOJ mice than in HIVJR-FLmC-unexposed mice (P = 0.0025). The weights of mesenteric lymph nodes of those HIVJR-FLmC-exposed hNOJ mice were also greater than those of HIVJR-FLmC-unexposed mice (P = 0.0005). When hNOJ mice were inoculated with HIVJR-FLmC-exposed hPBMC from Individual-B, significantly greater viremia was seen than in cell-free HIVJR-FLmC-inoculated hNOJ mice as examined on day 7. In the lymph nodes of those mice inoculated with HIVJR-FLmC-exposed hPBMC from Individual-B, a substantial number of Individual-B's HIVJR-FLmC-infected cells were identified together with Individual-A's cells as examined on day 14. The present HIVJR-FLmC-infected mouse model represents the first system reported using traceable HIVJR-FLmC and human target cells, not using SIV or simian cells, which should be of utility in studies of early-phases of HIV-1 transmission and in evaluating the effects of potential agents for post-exposure and pre-exposure prophylaxis.
AB - We attempted to elucidate early-phase dynamics of HIV-1 infection using replication-competent, red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL (HIVJR-FLmC) and NOD/SCID/Jak3-/- mice transplanted with Individual-A's human peripheral blood mononuclear cells (hPBMC)(hNOJ mice). On day 7 following HIVJR-FLmC inoculation, mCherry-signal-emitting infection foci were readily identified in the subserosa of 10 of 10 HIVJR-FLmC-inoculated hNOJ mice, although infection foci were not located without the mCherry signal in unlabeled HIV-1JR-FL-inoculated mice (n = 6). Even on day 14, infection foci were hardly located in the unlabeled HIV-1JR-FL-inoculated mice, while in all of 7 HIVJR-FLmC-inoculated hNOJ mice examined, mCherry-signal-emitting lymph nodes were easily identified, in which active viral replication was present. On day 14, a significantly larger number of mesenteric lymph nodes were seen in HIVJR-FLmC-exposed hNOJ mice than in HIVJR-FLmC-unexposed mice (P = 0.0025). The weights of mesenteric lymph nodes of those HIVJR-FLmC-exposed hNOJ mice were also greater than those of HIVJR-FLmC-unexposed mice (P = 0.0005). When hNOJ mice were inoculated with HIVJR-FLmC-exposed hPBMC from Individual-B, significantly greater viremia was seen than in cell-free HIVJR-FLmC-inoculated hNOJ mice as examined on day 7. In the lymph nodes of those mice inoculated with HIVJR-FLmC-exposed hPBMC from Individual-B, a substantial number of Individual-B's HIVJR-FLmC-infected cells were identified together with Individual-A's cells as examined on day 14. The present HIVJR-FLmC-infected mouse model represents the first system reported using traceable HIVJR-FLmC and human target cells, not using SIV or simian cells, which should be of utility in studies of early-phases of HIV-1 transmission and in evaluating the effects of potential agents for post-exposure and pre-exposure prophylaxis.
KW - Cell-associated HIV infection
KW - Early phase dynamics
KW - HIV propagation
KW - In vivo imaging
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U2 - 10.1016/j.antiviral.2017.03.027
DO - 10.1016/j.antiviral.2017.03.027
M3 - Article
C2 - 28392419
AN - SCOPUS:85019976723
VL - 144
SP - 83
EP - 92
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
ER -